We are investigating several aspects of genetically determined disease susceptibility of mice. One salmonella susceptible strain of mice, BSVS, develops low thymus dependent immune responses. Although this deficiency may contribute to the salmonella susceptibility, sequential backcross studies indicate that the contribution of a single allele from salmonella resistant A/J mice can render BSVS mice partially salmonella resistant without alleviating the deficiency in their T dependent immune responses. We are presently examining the mechanism of action by which this allele results in salmonella resistance. Also the effects of salmonella endotoxin on macrophage activation, immune responsiveness, and the levels of free iron in sera of BSVS mice are being studied. In studies with the immunodeficient CBA/N mouse we have demonstrated that "naturally occurring" anti-Streptococcal pneumoniae antibodies are of critical importance in the survival of mice experimentally infected with type 3 S. pneumoniae. Contrary to expectation these protective, naturally occurring antibodies do not appear to be directed to the type specific polysaccharide.